The subject of the invention is adenyl cyclase derivatives, their preparation by mutagenesis and their biological uses, in particular as vaccines.
Vaccinations against acute infections caused in vertebrates by pathogenic bacteria of the genus Bordetella or Bacillus anthracis generally require the utilization of virulent or attenuated whole bacteria.
However, such vaccines are not necessarily devoid of toxicity due to the nature of the diseases caused by these bacteria.
In fact, it is often proteins produced by bacteria, and not the bacteria themselves, which are responsible for the virulence. Even after bacterial death, these proteins may be responsible for many pathological effects.
In the pathology induced by Bordetella pertussis a filamentous hemagglutinin (FHA) as well as two toxins lead to an unregulated increase in the production of cyclic AMP in the host cells. These toxins are the pertussis toxin (Ptx or LPF) which activates the cyclase of the host, and the adenyl cyclase, activated by calmodulin (AC).
Finally, a hemolysin is associated with the adenyl cyclase.
The adenyl cyclase of B. pertussis was called cyclolysin to point out this fact.
In the light of these observations, the inventors have investigated vaccination agents in which the bacteria of the virulent or attenuated strains are not longer involved, but rather the proteins produced, are modified in an appropriate manner in order to destroy their original toxicity. In particular, adenyl cyclase has been investigated in this respect.